Increased BNP and NT-proBNP blood concentrations are associated with the severity and mortality in heart failure (HF) patients. In several studies the titration of drug treatment to reduce NT-proBNP levels in patients suffering from HF was investigated (Wasywich, et al. Changes in tissue-Doppler echocardiographic assessment of left ventricular filling during NT-proBNP guided heart failure treatment titration: a pilot study. Heart Lung and Circulation 2009; 18:38-44; Mant, et al. Identification and guided treatment of ventricular dysfunction in general practice using blood B-type natriuretic peptide. British Journal of General Practice 2008; 58:393-9; Davis, et al. Introduction of metoprolol increases plasma B-type cardiac natriuretic peptides in mild, stable heart failure. Circulation 2006; 113:977-85, Beck-da-Silva, et al. BNP-guided therapy not better than expert's clinical assessment for beta-blocker titration in patients with heart failure. Congestive Heart Failure 2005; 11:248-53; quiz 254-5).
It has been investigated whether vasoactive biomarkers and their precursors and fragments thereof stratify patients exhibiting a positive effect due to a specific medication. For example, the use of NT-proBNP for stratification of HF patients for medication was presented in the PRIMA-Study at the ACC Congress Orlando (29 Mar. 2009). Moreover, the utility of NT-proBNP measurements to identify patients with enhanced benefit from clopidogrel therapy was investigated by Tang et al., but no NT-proBNP subgroup could be identified with an overproportional benefit from clopidogrel therapy (Tang et al. Risk stratification for patients undergoing nonurgent percutaneous coronary intervention using N-terminal pro-B-type natriuretic peptide: a Clopidogrel for the Reduction of Events During Observation (CREDO) substudy. American Heart Journal 2007; 153:36-41). Kropp et al. hypothesized that NT-proBNP could be used as a marker for the tolerability and safety of antipsychotic drugs. (Kropp, et al. N-terminal fragment of B-type natriuretic peptide (NT-proBNP), a marker of cardiac safety during antipsychotic treatment. Annals of General Psychiatry 2005; 4:10). In addition, it has been contemplated that other neuroendocrine markers, e.g. AVP, ET-1, Big-ET-1, [NT-pro]ANP and [NT-pro]BNP, may be of value in the choice and titration of medical treatment for an individual patient in the future (Kjaer 2000; Videnskab og Praksis 162:5910-3). For example, it has been shown that elevated ANP levels before treatment with the beta-blocker carvedilol are predictive for reductions of mortality, and ANP and BNP are predictive for reductions of hospital admission in patients with chronic stable heart failure (Richards et al. Neurohumoral prediction of benefit from carvedilol in ischemic left ventricular dysfunction. Australia-New Zealand Heart Failure Group. Circulation 1999; 99:786-92). In contrast to the cardiac peptides, higher plasma levels of Arg-Vasopressin (AVP) did not predict benefit from carvedilol in this study. In addition the same study group revealed, that carvedilol reduced mortality and heart failure in patients with chronic ischemic left ventricular dysfunction exhibiting a higher pre-treatment plasma NT-proBNP and adrenomedullin (ADM) (Richards et al. Plasma N-terminal pro-brain natriuretic peptide and adrenomedullin—prognostic utility and prediction of benefit from carvedilol in chronic ischemic left ventricular dysfunction. Journal of the American College of Cardiology 2001; 37:1781-7). However, patients were stratified according to peptide concentrations below and above median and a beneficial effect of carvedilol was not apparent until 300 days after treatment initiation, indicating that elevated plasma levels of the measured peptides may only predict a long-term benefit of the Beta-blocker carvedilol. Swedberg et al. demonstrated, that markedly elevated levels of ANP before ACE inhibitor treatment (namely elanapril) were related to reductions in mortality levels in patients with severe congestive heart failure in NYHA class IV (Swedberg et al. Hormones regulating cardiovascular function in patients with severe congestive heart failure and their relation to mortality. CONSENSUS Trial study group. Circulation 1990; 82:1730-6). Again, patients were stratified according to peptide concentrations below and above median in this study. A beneficial effect of elanapril was demonstrated for mortality after 6 months.
In the patent application WO 2009/123730 methods for diagnosis and prognosis of pulmonary hypertension are described. A variety of markers has been suggested.